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The following is a summary of “Impact of attaining aggressive vs. conservative PK/PD target on the clinical efficacy of beta-lactams for the treatment of Gram-negative infections in the critically ill patients: a systematic review and meta-analysis,” published in the April 2024 issue of Critical Care by Gatti al.
Researchers started a retrospective study to assess the clinical impact of aggressive versus conservative beta-lactam PK/PD targets for treating Gram-negative infections in critically ill patients while identifying factors associated with failing to achieve aggressive targets.
They conducted separate searches on PubMed-MEDLINE and Scopus databases (December 23, 2023) to find studies comparing the effects of achieving aggressive versus conservative PK/PD targets on beta-lactam efficacy. Independent predictors of failure were evaluated to meet aggressive PK/PD targets. Aggressive PK/PD targeting involved maintaining 100% fT4xMIC, with clinical cure rate as the primary outcome. A meta-analysis combined ORs from studies adjusting for confounders using a random-effects model with an inverse variance method.
The results showed 20,364 articles screened, and 21 observational studies were included in the meta-analysis (N = 4833; 2193 targeted aggressively vs. 2640 targeted conservatively). Achieving aggressive PK/PD targets was linked to a significantly higher clinical cure rate (OR 1.69; 95% CI 1.15–2.49) and reduced risk of beta-lactam resistance development (OR 0.06; 95% CI 0.01–0.29). Factors such as male gender, body mass index > 30 kg/m2, augmented renal clearance and MIC above the clinical breakpoint were significant independent predictors of failure in achieving aggressive PK/PD targets, while prolonged/continuous infusion of beta-lactams was found to be a protective factor. The risk of bias was moderate in 19 studies and severe in the remaining 2.
Investigators concluded that aggressive beta-lactam PK/PD targets in critical patients improved clinical outcomes and provided a tool to identify those at high risk of failing to reach these targets.
Source: ccforum.biomedcentral.com/articles/10.1186/s13054-024-04911-5
